1. IB BIOLOGY Option A.5
Neuropharmacology

2. Interactions at the Synapse
Action potential causes flood of Ca2+ ions release of NT at cleft

3. Excitatory and Inhibitory NTs
Ach-excitatory NT generates AP
Increase permeability of post-synaptic neuron to + ions
Na+ floods in  depolarizedAP
GABA- inhibitory NT
Inhibits AP
Cause hyperpolarization harder for AP to be generated
Binds to receptor Cl- move in neuron or K+ to move out of post synaptic neuron

4. Modulation of Synaptic Transmission
Fast acting NTs:
Affect target cell in 1 millisecond of binding to receptor
Ex: Glutamate, GABA
Slow acting NTs:
Affect target cell in hundreds of milliseconds or up to a minute
Act on second messenger molecule, more time consuming
Neuromodulators
Released in CSF modulate FA NTs
Regulate efficiency of NT release
Regulate efficiency of receptor
Ex: dopamine, serotonin, acetylcholine

5. Memory and Learning FA and SA NTs affect learning and memory.
Experiment with Aplysia: pg 548
Short term process (learning) vs. long term process (memory)
Long term needs synthesis of proteins
Proteins change form and function of synapse memory
Stronger, long lasting stimulus needed for long term

7. Cholinergic Receptors
Receptors for Ach- excitatory NT
Part of parasympathetic NS (business as usual)
Acetylcholine esterase breaks down Ach after release at synapse to keep neuron from continually firing
Nicotine binds to these receptors

9. Adrenergic Receptors Receptors for Noradrenaline
Part of parasympathetic NS- (fight or flight)
Cocaine and amphetamines affect this receptor

11. Excitatory Drugs (Stimulants)
Cocaine, amphetamines, MDMA
Increase nerve transmission

12. Inhibitory Drugs (Sedatives)
Alcohol, THC, benzodiazepines, opiates
Decrease nerve transmission

13. Drugs can act on synapses by:
1. Blocking a receptor for an NT
2. Blocking release of an NT
3. Enhancing release of an NT
4. Enhancing an NT by mimicking an NT (analog)
5. Blocking removal of an NT, thus enhancing its effect.

14. Excitatory Drugs Nicotine
Mimics Ach, attaches and changes the cholinergic receptor
Ach is normally broken down in synapse by Ach esterase, but body cannot break down nicotine
Nicotine excites post-synaptic neuron to release Dopamine(Da), causing feelings of pleasure.

16. Excitatory drugs, cont. Cocaine
Stimulates transmission at adrenergic receptors
Increases alertness, euphoria
Also increases release of Da
Blocks removal of Da, which causes build-up and overstimulation of post-synaptic neuron
Increases feelings of reward and euphoria

18. Excitatory drugs, cont. Amphetamine
Stimulates transmission at adrenergic synapses increasing alertness and euphoria
Passes directly into the nerve cells, which carry DA and NA, moves DA and NA vesicles of pre-synaptic neuron for release in the synaptic cleft.
DA and NA normally removed by enzymes, but amphetamine interferes with this process
Result- more alertness and more euphoria

20. Excitatory drugs, cont. MDMA Structurally related to amphetamines
Causes extra release of serotonin (Se)
Cell bodies of Se neurons are in brainstem and have an axon network in the brain

22. Excitatory drugs, cont. MDMA mechanism of action-
Presynaptic neuron releases Se
Receptor of postsynaptic neuron activated by Se
A SERT (Se transport) vesicle on presynaptic neuron takes up extra Se
MDMA forces Se axons to release a lot of Se
When SERT catches up depression results
Se levels can become depleted

23. Excitatory drugs, cont. MDMA and Dopamine
Se depleted, SERT receptor is empty
DA enters SERT receptor by mistake
DA broken down, products are toxic to Se producing neurons
Neurotoxicity causes long-term brain cell damage

25. Inhibitory Drugs Benzodiazepines
Ex. Valium, used for seizures in epileptics
Modulate GABA
GABA binds to postsynaptic neuron causing Cl- to enter, result is hyperpolarization of neuron
Increase binding of GABA, increasing inhibitory signals

27. Inhibitory drugs, cont. Alcohol
Increased binding of GABA to postsynaptic neuron
Decreases activity of glutamate, an excitatory NT
Overall sedative effect results
Increases the release of DA, and stops activity that breaks down DA at synapse
Affects cerebellum coordination and reflexes
Affects the limbic system memory

29. Inhibitory drugs, cont. THC (tetrahydrocannabinol)
Main psychoactive ingredient in marijuana
Mimics anandamide, NT involved with memory
Binds to cannabinoid receptors hyperpolarizes neurons
Body breaks down anandamide, but not THC
Disrupts short term memory in humans
“relaxed and mellow” feelings, also paranoia and panic
Dilates pupils
Problems with learning, memory, coordination, problem solving

30. https://dotsub.com/view/d5638865-f253-4f11-9928-763ee68abbcc

31. Anesthetics: Used by doctors and dentists Novocain- local anesthetic
Blocks nerve transmission to pain centers
Na+ rushes in neurons pain felt
Block Na+ no pain
Drug induced insensitivity

33. Anesthetics, cont. General anesthesia-
Modifies function of gated ion channels
Binds directly to ion channels
Synaptic block:
Reduces presynaptic Ca2+ entry, reducing NT release
Increases postsynaptic Cl- entry and increases outward K+
Conduction block:
Reduces axonal Na+ entry which results in failure of AP propagation

35. Endorphins Discovered while studying opium addiction
Receptors for heroin, morphine and other opiates in brain cells
Endorphins are CNS NTs that have pain relieving properties.
Released by pituitary gland during stress, injury or exercise
Small peptides that bind to opiate receptors
Block transmission of pain impulses
Bind to receptors of neurons involved with pain perceptionblock release of NTs

37. Addiction Addictive drugs: Body develops tolerance: Addiction is:
Alcohol, tobacco, psychoactive drugs, pharmaceuticals
Take to alleviate symptoms:
Mental illness or for pleasure
Body develops tolerance:
Needs more drugs to produce desired effects.
Addiction is:
Chemical dependency on drugs where the drug has “re-wired” the brain so that it becomes an essential biochemical for the body

38. Addiction Series

39. https://www. youtube. com/watch

40. Withdrawal Symptoms opposite of euphoria Alcohol withdrawal:
Anxiety, depression and cravings
Alcohol withdrawal:
Seizures and delerium tremens (shaking)
Can be fatal
Inhaled drugs damage lung tissue
Kidney disease can develop
High risk behaviors:
Sharing needles
Unprotected sexual relations
Risk for HIV, hepatitis B and C

41. Genetic Predisposition
Twin studies:
Identical twins- 100% genetically identical
Fraternal twins- 50% genetically identical
Male twin studies give support to genetic component
Rats
Genetically manipulated to prefer alcohol
Had 20% lower dopamine levels
Non-alcohol rats consumed far less ethanol in studies

42. Social Factors Family of child Parenting skills
Mental health of family members
Peer pressure:
High in adolescents, lower in adults
Users teach new users
Introducing new drug into culture
British opium into China- disaster
Heroin-disaster for US
Saudi Arabia forbids alcohol, so its not a social problem there
Addiction more likely if drugs are cheap and easily available

43. Dopamine Secretion Addiction: More of drug is needed to feel “normal”
Dopamine receptors constantly being stimulated
Decreases the number of receptors
Receptors that remain become desensitized: tolerance
More of drug is needed to feel “normal”
Neuroadaptive change produces addiction
Glutamate: oversees the learning and memories that lead to drug seeking behaviors